Depression is among the most prevalent of all psychiatric disorders. It is critical, therefore, that we identify factors involved in the maintenance of depression and factors that impede recovery from this disorder. In a series of behavioral investigations we found depressed individuals to demonstrate biased attentional processing of negative stimuli only in response to prolonged stimulus exposure durations that permit elaboration of the material. Although we also found depressed individuals to exhibit impaired processing of positive stimuli, we demonstrated consistently that greater physiological reactivity and neural activation in response to positive stimuli predicts improved functioning of depressed individuals over the following year. Working to integrate these results has led us to both broaden and refine cognitive theories of depression to include a consideration of the roles of: (a) failure to disengage from negative stimuli;(b) inhibitory dysfunction affecting working memory;(c) long-term memory for emotional material;(d) responsivity to positive stimuli;and (e) patterns of neural activation in response to emotional stimuli and in the regulation of negative affect. In focusing on these constructs, we are gaining a more comprehensive understanding of precisely how cognitive and biological dysfunction can lead to emotional dysregulation and sustained negative affect, hallmark symptoms of depression. We propose a series of studies designed to test an integrative formulation of depression in which we posit different roles for the processing of negative and positive stimuli. We propose that depressed persons experience difficulty disengaging from, and inhibiting elaborative processing of, negative stimuli. We posit further that this inhibitory difficulty increases the likelihood of rumination, which in turn, leads to sustained negative affect. In addition, the attenuated processing by depressed individuals of positive stimuli impairs their ability to use positive memories or information to repair these negative affective states. Indeed, we posit that those depressed individuals who are able to engage most strongly with positive stimuli will recover from depression most quickly. Finally, we propose a series of investigations designed to elucidate the patterns of neural activation that are associated with each of these processes. Findings from these studies will represent important contributions to the continued development of an integrative psychobiological theory of depression.